The Current State of Rett Research

The last few years has brought unprecedented attention to Rett Syndrome by academic scientists, researchers and executives of pharmaceutical and biotech companies and more recently, life sciences investors. The interest stems from the advantages enjoyed by the Rett field: a known and single genetic cause, expectation of reversibility, NIH funded natural history study and Rett clinics with significant patient populations.

The graphic below encapsulates the various approaches that are currently being pursued.

Since Rett Syndrome is caused by defective MECP2 it stands to reason that approaches that attack the root cause, MECP2 itself, hold the greatest promise of significantly improving symptoms. Therefore approaches such as activating the silent MECP2, gene therapy and protein replacement can be classified as potentially curative approaches.

On the other hand therapeutic interventions that are downstream of MeCP2 will likely improve a symptom or subset of symptoms. These approaches are treatments rather than cures.

Unpublished Phase 2 results announced by Neuren show drug to be safe and well tolerated.

Neuren indicates preliminary efficacy signals suggestive of benefit. Further studies will be necessary to ​​definitively establish whether or not the drug confers clinical benefit.​

Drug does not address underlying cause of disorder so impact may be restricted to subset of symptoms and/or individuals

No published animal studies

Not approved drug yet – longer development timeline

No data for use in children

Statins

Addresses imbalances in cholesterol synthesis that may contribute to Rett symptoms

Monica Justice (P)

Sasha Djukic(P2)

Cholesterol pathway is well studied

FDA approved and cheap

Many drugs that work on cholesterol pathway, beyond statins, are available for testing.

Drug does not address underlying cause of disorder so impact may be restricted to subset of symptoms and/or individuals

Unknown whether only a certain age group will benefit

Unknown to what degree cholesterol pathway is disrupted in Rett

Topoisomerase inhibitors or other drugs that correct long gene expression

MeCP2 appears to turn down protein production of physically long genes. In Rett where MeCP2 is not working properly long genes are upregulated. A drug that lowers expression of long genes can therefore rebalance the situation.

Drugs are already available to facilitate pilot studies testing feasibility and efficacy of treatment in mice (toxicity of these drugs are likely an issue that will have to be addressed before use in humans, see limitations).

Drug may not replace every critical function of MeCP2 so impact may be restricted to subset of symptoms